A Novel DNA Aptamer Targeting S100P Induces Antitumor Effects in Colorectal Cancer Cells

Sun, Wenjing; Luo, Lixiang; Fang, Daoquan; Tang, Tianbin; Ni, Wuhua; Dai, Bichun; Sun, Hongwei; Jiang, Lei

doi:10.1089/nat.2020.0863

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…Evidence for S100P being a viable anticancer target is also provided by an aptamer approach in colorectal cancer with high affinity to and selectivity for S100P protein. This aptamer has shown high activity in cells and in a xenograft model for this disease [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

et al. 2023

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The naphthalene diimide compound QN-302, designed to bind to G-quadruplex DNA sequences within the promoter regions of cancer-related genes, has high anti-proliferative activity in pancreatic cancer cell lines and anti-tumor activity in several experimental models for the disease. We show here that QN-302 also causes downregulation of the expression of the S100P gene and the S100P protein in cells and in vivo. This protein is well established as being involved in key proliferation and motility pathways in several human cancers and has been identified as a potential biomarker in pancreatic cancer. The S100P gene contains 60 putative quadruplex-forming sequences, one of which is in the promoter region, 48 nucleotides upstream from the transcription start site. We report biophysical and molecular modeling studies showing that this sequence forms a highly stable G-quadruplex in vitro, which is further stabilized by QN-302. We also report transcriptome analyses showing that S100P expression is highly upregulated in tissues from human pancreatic cancer tumors, compared to normal pancreas material. The extent of upregulation is dependent on the degree of differentiation of tumor cells, with the most poorly differentiated, from more advanced disease, having the highest level of S100P expression. The experimental drug QN-302 is currently in pre-IND development (as of Q1 2023), and its ability to downregulate S100P protein expression supports a role for this protein as a marker of therapeutic response in pancreatic cancer. These results are also consistent with the hypothesis that the S100P promoter G-quadruplex is a potential therapeutic target in pancreatic cancer at the transcriptional level for QN-302.

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Section: Discussionmentioning

confidence: 99%

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

et al. 2023

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“…AptS100P-1 also prevented S100P-expressing CRC cells from migrating and transitioning from epithelial to mesenchymal cells by suppressing the expression of EMT protein and overturning the EMT process. The findings indicate that using AptS100P-1 to target S100P could be a viable treatment strategy for CRC [82]. Figure 4 below mentions the different types of molecular targets targeted by aptamers as potential cancer treatments in GI cancers and Table 4 below mentions all the relevant functions and molecular mechanisms of aptamers associated with molecular targets in GI cancers.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…As a result, S100P could be a promising molecular target for CRC treatment. For instance, Sun et al [82] used the SELEX technique and high-throughput sequencing to create a new DNA aptamer targeting S100P (AptS100P-1). AptS100P-1 had a significant affinity for S100P protein, as evidenced in the binding experiment.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…Lastly, S100P functions as a Ca 2+ binding protein in calcium-dependent signal transduction pathways involved in various biological activities. It has been shown to play a crucial role in promoting cell proliferation, invasion, and metastasis in CRC tissues and is overexpressed in CRC 82 . As a result, S100P could be a promising molecular target for CRC treatment.…”

Section: Aptamers Bind To Different Molecular Targets As a Potential ...mentioning

confidence: 99%

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Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms

Goh¹,

Stephen²,

Wu³

et al. 2023

J. Cancer

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Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.

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Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy

Uinarni,

Oghenemaro,

Menon

et al. 2024

Cell Biochem Biophys

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A Novel DNA Aptamer Targeting S100P Induces Antitumor Effects in Colorectal Cancer Cells

Cited by 5 publications

References 28 publications

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

The Potent G-Quadruplex-Binding Compound QN-302 Downregulates S100P Gene Expression in Cells and in an In Vivo Model of Pancreatic Cancer

Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms

Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy

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